PhotoDynamic Therapy (PDT) is a relatively new method useful for treating various types of malignant and non-malignant hyperproliferative diseases, for example, cancers and hyperplasias. Certain photodynamic compounds, called photosensitizers (PS), have the ability to selectively accumulate in hyperproliferative tissue as compared to normal tissue. When administered, these PS accumulate in hyperproliferative tissue and absorb light. Light absorption causes the PS to destroy hyperproliferative tissue. Activated PS tissue destruction is known as PDT.
The PS are administered to the subject by a suitable method in order to accumulate in the hyperproliferative tissue. Photosensitizers are activated by electromagnetic radiation, for example, laser radiation delivered through fiber optics to cause cytotoxicity in hyperproliferative tissue, such as, the production of singlet oxygen. The oxygen radicals are toxic to the cells and induce cellular destruction via necrosis or apoptosis.
Unfortunately, current PDT approaches suffer from several well-known, and widely recognized shortcomings. For example, certain therapeutic approaches require the invasive placement of a light source in or adjacent to the abnormal tissue to be treated. The invasive nature of such procedures is undesirable for obvious reasons, for example, the need for local or general anesthetics, higher risk of infection, increased pain and discomfort, and longer recovery times. Additional procedures that are currently available require the co-administration (i.e., either simultaneous or sequential) of the PS agent with one or more immuno-adjuvants and/or immunopotentiators. The use of immunoadjuvants or immunopotentiators is problematic because they can have detrimental side-effects, including, for example, severe immunogenic responses, and adverse molecular interactions within a patient. Such adverse events can lead to longer and more costly patient treatment and recovery durations.
In U.S. Pat. No. 5,865,840 by Chen, a plurality of PDT treatments are disclosed that follow at least one initial treatment, characterized by an increase in neutrophil count achieved by administering a myeloid colony stimulating factor after the first treatment. The light source used here is either implanted in the abnormal tissue or disposed adjacent to the abnormal tissue, which are additional and invasive steps that could cause discomfort.
U.S. Patent Application 2005/0187207 by Curry et al. (“Curry”) describes an immuno-adjuvant PDT to treat and prevent metastatic cancer. This therapy involves the administration of one or more PS and one or more immuno-adjuvants followed by irradiation with suitable wavelength. Selection of an in-proper immuno-adjuvant and interactions within a patient can lead to complex problems.
U.S. Patent Application 2002/0004053 by Biel et al. prescribes administration of an immunologic adjuvant to enhance a nonspecific immune system response, similar to Curry. Subsequently, the area is treated with appropriate radiation to destroy abnormal cells. Photosensitizer administration to the target tumor may spread to tissue surrounding the tumor causing excessive, non-therapeutic tissue damage. Repeated immuno-adjuvant administration could be associated with side effects and lengthy treatment duration.
U.S. Pat. No. 6,290,712 by Nordquist et al. discloses combination therapy of PDT and an immunopotentiator to stimulate the immune system. The immunopotentiator is a necessary component to stimulate an immune system inflammatory response.
U.S. Pat. No. 6,495,585 by Bellnier et al., discloses a method including the following steps: injecting a PS having a selective uptake in hyperproliferative tissue and activation at a particular light frequency; injecting xanthonone-4-acetic acid or a Group I metal, Group II metal or quaternary salt near the time of maximum uptake of the PS in hyperproliferative tissue; and exposing the hyperproliferative tissue to light that activates the PS. The method is stated to locally treat malignant tumors and stimulate tumor immunity resulting in the control of primary tumors and occult metastases by combining PDT with an additional agent for modifying a biological response.
As discussed above, certain strategies exist that attempt to stimulate the immune system in order to improve the efficacy of PDT. However, these attempts have all been characterized by the combined use of PDT and immunopotientators to stimulate an immune response. The present invention is advantageous over the current methods as it provides for improved PDT without the need for introducing an immunopotientator into the body, thereby eliminating concerns about the immunopotientator's adverse effects.